Hypertension remains one of the leading modifiable risk factors for cardiovascular morbidity and mortality globally [1]. According to the World Health Organization, over 1.28 billion adults worldwide suffer from elevated blood pressure, with the majority being undiagnosed or inadequately managed [2]. While the traditional etiological understanding of hypertension has focused on genetic predisposition, lifestyle factors, and environmental influences, recent advances in molecular biology and microbiome science have introduced the gut microbiota as a potential key player in the pathogenesis of hypertension [3][4]. The human gastrointestinal tract harbors trillions of microorganisms, collectively known as the gut microbiota, which maintain a delicate symbiotic relationship with the host [5]. This microbiota plays a pivotal role in nutrient metabolism, immune modulation, maintenance of the intestinal barrier, and production of bioactive compounds such as short-chain fatty acids (SCFAs) [6]. Disruption of this balance a condition termed “dysbiosis” has been increasingly associated with systemic inflammation, metabolic disturbances, and cardiovascular diseases, including hypertension [7].

Several animal and human studies have demonstrated that hypertensive individuals exhibit a distinct gut microbial signature compared to normotensive individuals [8]. Specifically, a reduction in SCFA-producing bacteria such as Faecalibacterium prausnitzii, Roseburia, and Lactobacillus, alongside an increase in opportunistic pathogens such as Klebsiella, Enterobacter, and Desulfovibrio, has been reported. SCFAs like butyrate and propionate are known to exert anti-inflammatory effects, improve endothelial function, and regulate blood pressure via G-protein coupled receptors. Their decline, therefore, may contribute to endothelial dysfunction and increased vascular tone [9] [10]. Moreover, microbial-derived metabolites such as trimethylamine-N-oxide (TMAO) have also been linked to vascular inflammation and atherosclerosis, both of which are closely related to hypertension [11]. Another mechanism through which dysbiosis may influence blood pressure is via increased gut permeability ("leaky gut"), allowing the translocation of bacterial endotoxins (e.g., lipopolysaccharide) into systemic circulation, thereby triggering chronic low-grade inflammation, an established contributor to hypertension [12]. Recent studies utilizing 16S rRNA sequencing and metagenomic analysis have consistently found reduced alpha diversity in hypertensive populations, indicating a less diverse and possibly less resilient microbiota [13]. In addition to compositional shifts, functional alterations in the microbiome's metabolic pathways have also been noted in hypertensive subjects. However, there remains a paucity of large-scale, region-specific studies examining these associations in diverse human populations [14].

Objective

To evaluate the association between gut microbiota dysbiosis and clinical parameters in hypertensive patients.

A cross-sectional analytical study enrolling 181 adult patients, including hypertensive individuals and age-matched normotensive controls, using non-probability consecutive sampling.

Inclusion Criteria:

• Adults aged 30 to 65 years
• Diagnosed with primary hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg)
• Not on antibiotics or probiotics for the past 3 months
• Able to provide informed consent

Exclusion Criteria:

• History of secondary hypertension or gastrointestinal disease
• Recent hospitalization or surgery (within 3 months)
• Immunosuppressive therapy or chronic steroid use
• Pregnancy or lactation

Data Collection

After obtaining informed consent, detailed demographic and clinical data were recorded, including age, gender, BMI, blood pressure, smoking status, medication use, and comorbidities. Fecal samples were self-collected by participants using sterile kits and stored at −80°C until processing. Microbial DNA was extracted from stool samples, and 16S rRNA gene sequencing targeting the V3-V4 region was performed to characterize microbial diversity and composition. Key microbial metrics such as alpha diversity (Shannon index) and relative abundance of dominant bacterial taxa were calculated. Serum CRP and fasting glucose levels were also measured to assess systemic inflammation and metabolic status.

Statistical Analysis

Data analysis was performed using SPSS version 17 and R for microbiome-specific computations. Continuous variables such as age, blood pressure, microbial diversity indices, and inflammatory markers were expressed as mean ± standard deviation and compared between hypertensive and normotensive groups using the independent t-test. A p-value < 0.05 was considered statistically significant.

The hypertensive group (n=110) had a slightly higher average age (58.3 years) compared to the normotensive group (56.1 years), though this difference was not statistically significant (p=0.08). A greater proportion of hypertensive patients were male (58.2% vs. 50.7%), but again, this was not significant (p=0.14). However, hypertensive individuals had a significantly higher body mass index (BMI of 29.8 vs. 27.3; p=0.002) and a greater prevalence of diabetes (40.9% vs. 22.5%; p=0.01). The differences in systolic (151.2 mmHg vs. 121.6 mmHg) and diastolic (94.7 mmHg vs. 78.3 mmHg) blood pressure were highly significant (p<0.001), confirming the clinical distinction between the two groups.

Table 1: Demographic and Clinical Characteristics

Hypertensive patients exhibited significantly reduced gut microbial diversity. The mean Shannon index was 3.10 compared to 3.75 in normotensive individuals (p<0.001), indicating lower species richness and evenness. Similarly, the Simpson index was lower in hypertensives (0.72 vs. 0.84; p<0.001), and they had fewer observed operational taxonomic units (OTUs) (183 vs. 212; p<0.001). These findings highlight substantial dysbiosis in the gut microbiota of patients with hypertension.

Table 2: Alpha Diversity Indices

Hypertensive patients showed a significant reduction in beneficial genera like Faecalibacterium (8.4% vs. 12.1%, p<0.001) and Roseburia (5.6% vs. 8.7%, p<0.001), both of which are associated with anti-inflammatory SCFA production. Conversely, pro-inflammatory genera such as Enterobacter and Klebsiella were notably elevated in hypertensives (6.8% and 4.9%, respectively) compared to normotensives (3.3% and 2.1%), with both differences being statistically significant (p<0.001). These microbial shifts suggest a pathogenic microbial signature in hypertension.

Table 3: Relative Abundance of Key Genera

There was a moderate inverse correlation between gut microbial diversity (Shannon index) and systolic blood pressure (r = -0.41, p<0.001), diastolic blood pressure (r = -0.36, p<0.001), and CRP levels (r = -0.35, p=0.004), indicating that lower diversity is associated with worse clinical and inflammatory profiles. A weaker but still significant correlation was also found with fasting glucose levels (r = -0.29, p=0.012), linking dysbiosis to metabolic dysfunction.

Table 4: Correlation Between Microbial Diversity and Clinical Parameters

In multivariate analysis, a low Shannon index independently predicted hypertension with an adjusted odds ratio (OR) of 2.85 (95% CI: 1.57–5.18, p<0.001). High Enterobacter abundance was also a strong predictor (OR: 2.41, p=0.004), while elevated BMI modestly increased the odds of hypertension (OR: 1.89, p=0.03). Age over 60 and male gender were not statistically significant predictors in this model (p=0.22 and 0.32, respectively).

Table 5: Multivariate Logistic Regression Predicting Hypertension

This study demonstrated a strong association between gut microbiota dysbiosis and hypertension in a sample of 181 participants, where 110 were hypertensive and 71 normo-tensive. The hypertensive group showed significantly lower microbial diversity, as evidenced by a Shannon index of 3.10 ± 0.6 compared to 3.75 ± 0.5 in normotensive individuals (p<0.001). Similar reductions were observed in the Simpson index (0.72 vs. 0.84, p<0.001) and observed OTUs (183 vs. 212, p<0.001), indicating a less diverse and less resilient gut ecosystem among hypertensive patients. These findings are consistent with previous research, which also reported a significant decline in alpha diversity in hypertensive cohorts, suggesting that reduced microbial diversity may impair homeostatic balance and promote inflammation [15]. Lower diversity is known to compromise the gut barrier and microbial production of beneficial metabolites, both of which play a role in cardiovascular regulation. In our study, the relative abundance of Faecalibacterium—a key SCFA (butyrate) producing genus was significantly reduced in hypertensives (8.4% vs. 12.1%, p<0.001), as was Roseburia (5.6% vs. 8.7%, p<0.001). These SCFA producers are known to maintain intestinal barrier integrity and modulate systemic inflammation. Previous research has similarly demonstrated a depletion of these genera in individuals with elevated blood pressure, indicating their central role in gut-vascular health [16][17].

Conversely, pro-inflammatory bacteria such as Enterobacter and Klebsiella were significantly enriched in hypertensive individuals (6.8% and 4.9%, respectively) compared to normotensive controls (3.3% and 2.1%, p<0.001). These genera produce endotoxins like lipopolysaccharide (LPS), which can trigger systemic inflammation, vasoconstriction, and endothelial dysfunction. These findings are corroborated by previous research that linked elevated LPS-producing bacteria with increased cardiovascular risk [18]. Correlation analysis in our study further validated these associations. The Shannon index was inversely correlated with systolic blood pressure (r = -0.41, p<0.001), diastolic blood pressure (r = -0.36, p<0.001), and CRP levels (r = -0.35, p=0.004), suggesting that microbial richness directly influences both vascular tone and systemic inflammation. This parallels previous research where similar negative correlations were found between microbial diversity and inflammatory/metabolic biomarkers [19]. Importantly, in multivariate logistic regression analysis, a low Shannon index remained a significant independent predictor of hypertension with an adjusted odds ratio (OR) of 2.85 (95% CI: 1.57–5.18, p<0.001), as did high Enterobacter abundance (OR = 2.41, p=0.004). Elevated BMI was also associated with hypertension (OR = 1.89, p=0.03), but age and gender were not significant predictors. These findings underscore the independent contribution of gut microbiota dysbiosis to hypertensive risk, consistent with previous research that identified these genera as potential biomarkers [20]. In conclusion, this study supports the hypothesis that gut microbial imbalance contributes to the pathogenesis of hypertension. The observed microbial signatures—characterized by reduced diversity, depletion of beneficial SCFA producers, and enrichment of pathogenic gram-negative genera suggest that microbiome-targeted strategies could be leveraged to modulate blood pressure. Further interventional studies are warranted to explore the therapeutic potential of probiotics, prebiotics, and dietary modifications in this domain.

It is concluded that gut microbiota dysbiosis is significantly associated with hypertension, characterized by reduced microbial diversity, diminished populations of beneficial SCFA-producing bacteria, and increased abundance of pro-inflammatory genera such as Enterobacter and Klebsiella. These microbial shifts correlate strongly with elevated blood pressure, systemic inflammation, and metabolic dysregulation. The study further identifies low microbial diversity and high Enterobacter levels as independent predictors of hypertension. These findings underscore the potential of the gut microbiota as both a biomarker and therapeutic target in the prevention and management of hypertension.

1. Li, Jing, Fangqing Zhao, Yidan Wang, Junru Chen, Jie Tao, Gang Tian, Shouling Wu et al. "Gut microbiota dysbiosis contributes to the development of hypertension."Microbiome 5 (2017): 1-19.
2. Yang, T., Santisteban, M. M., Rodriguez, V., Li, E., Ahmari, N., Carvajal, J. M., ... & Mohamadzadeh, M. (2015). Gut dysbiosis is linked to hypertension.hypertension, 65(6), 1331-1340.
3. Silveira-Nunes, Gabriela, Danielle Fernandes Durso, Luiz Roberto Alves de Oliveira Jr, Eloisa Helena Medeiros Cunha, Tatiani Uceli Maioli, Angélica Thomaz Vieira, Elaine Speziali et al. "Hypertension is associated with intestinal microbiota dysbiosis and inflammation in a Brazilian population."Frontiers in pharmacology 11 (2020): 258.
4. Yan, Qiulong, Yifang Gu, Xiangchun Li, Wei Yang, Liqiu Jia, Changming Chen, Xiuyan Han et al. "Alterations of the gut microbiome in hypertension."Frontiers in cellular and infection microbiology 7 (2017): 381.
5. Yu, Y., Mao, G., Wang, J., Zhu, L., Lv, X., Tong, Q., ... & Wang, G. (2018). Gut dysbiosis is associated with the reduced exercise capacity of elderly patients with hypertension.Hypertension Research, 41(12), 1036-1044.
6. Honour, J. W. (2015). Historical perspective: gut dysbiosis and hypertension.Physiological genomics, 47(10), 443-446.
7. Katsi, V., Didagelos, M., Skevofilax, S., Armenis, I., Kartalis, A., Vlachopoulos, C., ... & Tousoulis, D. (2019). GUT Microbiome-GUT dysbiosis-arterial hypertension: New horizons.Current hypertension reviews, 15(1), 40-46.
8. Zuo, Kun, Jing Li, Qiuhua Xu, Chaowei Hu, Yuanfeng Gao, Mulei Chen, Roumu Hu et al. "Dysbiotic gut microbes may contribute to hypertension by limiting vitamin D production."Clinical cardiology 42, no. 8 (2019): 710-719.
9. Richards, E. M., Pepine, C. J., Raizada, M. K., & Kim, S. (2017). The gut, its microbiome, and hypertension.Current hypertension reports, 19, 1-11.
10. De la Cuesta-Zuluaga, Jacobo, Noel T. Mueller, Rafael Álvarez-Quintero, Eliana P. Velásquez-Mejía, Jelver A. Sierra, Vanessa Corrales-Agudelo, Jenny A. Carmona, José M. Abad, and Juan S. Escobar. "Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors."Nutrients 11, no. 1 (2018): 51.
11. Li, Huijun, Bingdong Liu, Jie Song, Zhen An, Xiang Zeng, Juan Li, Jing Jiang, Liwei Xie, and Weidong Wu. "Characteristics of gut microbiota in patients with hypertension and/or hyperlipidemia: a cross-sectional study on rural residents in Xinxiang County, Henan Province."Microorganisms 7, no. 10 (2019): 399.
12. Santisteban, Monica M., Yanfei Qi, Jasenka Zubcevic, Seungbum Kim, Tao Yang, Vinayak Shenoy, Colleen T. Cole-Jeffrey et al. "Hypertension-linked pathophysiological alterations in the gut."Circulation research 120, no. 2 (2017): 312-323.
13. Oyama, Jun-ichi, and Koichi Node. "Gut microbiota and hypertension."Hypertension Research 5 (2019): 741-743.
14. Kang, Yongbo, and Yue Cai. "Gut microbiota and hypertension: From pathogenesis to new therapeutic strategies."Clinics and research in hepatology and gastroenterology 42, no. 2 (2018): 110-117.
15. Mashaqi, Saif, and David Gozal. "Obstructive sleep apnea and systemic hypertension: gut dysbiosis as the mediator?."Journal of Clinical Sleep Medicine 15, no. 10 (2019): 1517-1527.
16. Palmu, J., Salosensaari, A., Havulinna, A. S., Cheng, S., Inouye, M., Jain, M., ... & Niiranen, T. J. (2020). Association between the gut microbiota and blood pressure in a population cohort of 6953 individuals.Journal of the American Heart Association, 9(15), e016641.
17. Jin, Mengchao, Zhiyuan Qian, Jiayu Yin, Weiting Xu, and Xiang Zhou. "The role of intestinal microbiota in cardiovascular disease."Journal of cellular and molecular medicine 23, no. 4 (2019): 2343-2350.
18. Kim, S., V. Rodriguez, M. Santisteban, T. Yang, Y. Qi, M. Raizada, and C. Pepine. "6B. 07: Hypertensive patients exhibit gut microbial dysbiosis and an increase in TH17 cells."Journal of hypertension 33 (2015): e77-e78.
19. Dan, Xie, Zhang Mushi, Wang Baili, Lin Han, Wu Enqi, Zhao Huanhu, and Li Shuchun. "Differential analysis of hypertension-associated intestinal microbiota."International Journal of Medical Sciences 16, no. 6 (2019): 872.
20. Karbach, S. H., Schönfelder, T., Brandão, I., Wilms, E., Hörmann, N., Jäckel, S., ... & Wenzel, P. (2016). Gut microbiota promote angiotensin II–induced arterial hypertension and vascular dysfunction.Journal of the American Heart Association, 5(9), e003698.